Dataset Information

Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, Mycobacterium abscessus Isolates.

ABSTRACT: Purpose:The emergence of clarithromycin resistance is a challenge in treating Mycobacterium abscessus infections. Known mechanisms that contribute to intrinsic clarithromycin resistance focus on rrl gene-related mutations, but resistant clinical isolates often exhibit an inconsistent rrl genotype. Patients and Methods:In this study, 194 clinical Mycobacterium abscessus isolates were collected from patients with lung infections and the whole genome of each isolate was sequenced. A comprehensive examination of the molecular mechanisms underlying intrinsic clarithromycin resistance was performed, combining MIC determination, comparative genome sequence analysis and qRT-PCR. Results:Of the 194 isolates, 13 (6.7%) were clarithromycin resistant; only seven of these harbored a rrl 2270/2271 mutation. The remaining six resistant isolates did not exhibit a specific resistance-associated mutation in the clarithromycin target-site genes, rrl, rplC, rplD and rplV, or in the rrl modification gene erm(41). qRT-PCR analysis showed that the increased expression of the efflux pump genes, MAB_2355c, MAB_1409c and MAB_1846, as well as their positive regulatory gene whiB7, consistently correlated with increased clarithromycin resistance. The presence of efflux pump inhibitors significantly decreased the MIC of clarithromycin for nonsusceptible isolates, especially the intrinsic resistant isolates that exhibited no rrl 2270/2271 mutation. Conclusion:These findings indicate that efflux pumps play a prominent role in the intrinsic resistance of M. abscessus to clarithromycin, complementing other known resistance mechanisms.

SUBMITTER: Guo Q

PROVIDER: S-EPMC7024787 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, <i>Mycobacterium abscessus</i> Isolates.

Guo Qi Q Chen Jianhui J Zhang Shaoyan S Zou Yuzhen Y Zhang Yongjie Y Huang Dongdong D Zhang Zhemin Z Li Bing B Chu Haiqing H

Infection and drug resistance 20200212

<h4>Purpose</h4>The emergence of clarithromycin resistance is a challenge in treating <i>Mycobacterium abscessus</i> infections. Known mechanisms that contribute to intrinsic clarithromycin resistance focus on <i>rrl</i> gene-related mutations, but resistant clinical isolates often exhibit an inconsistent <i>rrl</i> genotype.<h4>Patients and methods</h4>In this study, 194 clinical <i>Mycobacterium abscessus</i> isolates were collected from patients with lung infections and the whole genome of ea ...[more]

PMID: 32104016

Similar Datasets

Project description:PURPOSE:Clarithromycin was considered the cornerstone for the treatment of Mycobacterium abscessus complex infections. Genetic resistance mechanisms have been described and many experts propose amikacin as an alternative. Nevertheless, clarithromycin has several advantages; therefore, it is necessary to identify the non-functional erm(41) allele to determine the most suitable treatment. The aims of this study were to characterize the molecular mechanisms of clarithromycin resistance in a collection of Mycobacterium abscessus complex isolates and to verify the relationship between these mechanisms and the antibiogram. MATERIALS AND METHODS:Clinical isolates of M. abscessus complex (n = 22) from 16 patients were identified using four housekeeping genes (rpoB, secA1, sodA and hsp65), and their genetic resistance was characterized by studying erm(41) and rrl genes. Nine strains were recovered from the clinical isolates and subjected to E-test and microdilution clarithromycin susceptibility tests, with readings at 3, 7 and 14 days. RESULTS:We classified 11/16 (68.8%) M. abscessus subsp. abscessus, 4/16 (25.0%) M. abscessus subsp. bolletii, and 1/16 (6.3%) M. abscessus subsp. massiliense. T28 erm(41) allele was observed in 8 Mycobacterium abscessus subps. abscessus and 3 Mycobacterium abscessus subsp. bolletii. One strain of M. abscessus subsp. bolletii had an erm(41) gene truncated and was susceptible to clarithromycin. No mutations were observed in rrl gene first isolates. In three patients, follow-up of initial rrl wild-type strains showed acquired resistance. CONCLUSIONS:Most clinical isolates of M. abscessus complex had inducible resistance to clarithromycin and total absence of constitutive resistance. Our findings showed that the acquisition of resistance mutations in rrl gene was associated with functional and non-functional erm(41) gene. Caution is needed when using erm(41) sequencing alone to identify M. abscessus subspecies. This study reports an acquired mutation at position 2057 of rrl gene, conferring medium-low clarithromycin constitutive resistance.

Dataset Information

Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, Mycobacterium abscessus Isolates.

Publications

Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical, <i>Mycobacterium abscessus</i> Isolates.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets